Li Ling, Lyu Xiao-Dong, Mi Rui-Hua, Ding Jing, Chen Lin, Wang Qian, Yin Qing-Song, Hu Jie-Ying, Fan Rui-Hua, Wei Xu-Dong
Department of Hematology, Henan Institute of Hematology, Zhengzhou, Henan Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Jun;21(3):601-6. doi: 10.7534/j.issn.1009-2137.2013.03.013.
This study was aimed to evaluate the frequencies and prognostic significance of the nucleophosmin 1 (NPM1) mutation, the fms-like tyrosine kinase 3 (FLT3) mutation and c-KIT mutation in acute myeloid leukemia (AML) and to explore their relevance to clinical characteristics, cytogenetics and survival. Genomic DNA from 78 newly diagnosed AML from August 2010 to October 2012 was screened by PCR and sequencing or capillary electrophoresis (CE) for NPM1, FLT3 and c-KIT mutations. The results showed that the incidence of NPM1 mutation was 14.1% in AML patients and 26.7% in normal karyotype AML patients. NPM1 mutant cases were significantly associated with old age (P < 0.05), high peripheral white cell count and platelet counts (P < 0.05) and low expression of CD34 (P < 0.05), but no statistic difference was found in sex, percentage of bone marrow blasts, Hb, expression of CD117 and HLA-DR, complete remission rate, overall survival and relapse rate (P > 0.05). The prevalences of FLT3-ITD and FLT3-TKD mutations were 11.5% (9/78) and 3.8% (3/78) respectively, and no one patient has both of the two mutations. Patients with FLT3-ITD mutation had higher white blood cell counts and percentage of in bone marrow blasts (P < 0.05), and lower overall survival (P < 0.05), more relative to normal karyotype (P < 0.05), while no statistic difference was found in sex, age, platelet count, Hb level, complete remission rate and relapse rate (P > 0.05). No statistic analysis was performed due to the cases of less FLT3-TKD mutation. C-KIT mutation accounts for 7.7% (6/78). Patients with C-KIT mutation had a higher percentage in abnormal karyotype (P < 0.05), and higher relapse rate (P < 0.05), and lower overall survival, whereas no statistic difference was found in sex, age, percentage of bone marrow blasts, peripheral blood cell count, complete remission rate (P > 0.05). It is concluded that the detection of NPM1, FLT3 and C-KIT mutations may contribute to guiding treatment and evaluating prognosis of patients with AML.
本研究旨在评估急性髓系白血病（AML）中核磷蛋白1（NPM1）突变、fms样酪氨酸激酶3（FLT3）突变和c-KIT突变的频率及预后意义，并探讨它们与临床特征、细胞遗传学及生存情况的相关性。采用聚合酶链反应（PCR）及测序或毛细管电泳（CE）技术，对2010年8月至2012年10月期间新诊断的78例AML患者的基因组DNA进行NPM1、FLT3和c-KIT突变检测。结果显示，AML患者中NPM1突变发生率为14.1%，正常核型AML患者中为26.7%。NPM1突变病例与老年（P<0.05）、外周血白细胞计数及血小板计数升高（P<0.05）和CD34低表达（P<0.05）显著相关，但在性别、骨髓原始细胞百分比、血红蛋白（Hb）、CD117及人类白细胞抗原-DR（HLA-DR）表达、完全缓解率、总生存率及复发率方面差异无统计学意义（P>0.05）。FLT3内部串联重复（FLT3-ITD）突变和FLT3酪氨酸激酶结构域（FLT3-TKD）突变的发生率分别为11.5%（9/78）和3.8%（3/78），无一例患者同时存在这两种突变。FLT3-ITD突变患者白细胞计数及骨髓原始细胞百分比更高（P<0.05），总生存率更低（P<0.05），相对于正常核型更常见（P<0.05），而在性别、年龄、血小板计数、Hb水平、完全缓解率及复发率方面差异无统计学意义（P>0.05）。因FLT3-TKD突变病例较少，未进行统计学分析。c-KIT突变占7.7%（6/78）。c-KIT突变患者异常核型比例更高（P<0.05），复发率更高（P<0.05），总生存率更低，而在性别、年龄、骨髓原始细胞百分比、外周血细胞计数、完全缓解率方面差异无统计学意义（P>0.05）。结论：检测NPM1、FLT3和c-KIT突变可能有助于指导AML患者的治疗及评估预后。
